摘要
目的：探讨第三代β受体阻滞剂卡维地洛对兔心肌梗死（MI）后胞外基质重构的作用及机制．方法：将36只新西兰大耳白兔随机分为MI组、MI＋卡维地洛组、假手术组，每组12只．采用结扎冠状动脉左室支建立MI模型，另以开胸后在相应部位挂线不结扎为假手术组．4wk后行血流动力学检查；测量体质量（BW）、左、右心室质量（LVW，RVW）；苦味酸-酸性品红染色检测非梗死区的胶原容积分数（CVF）；免疫组化检测基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）的表达，酶谱法测定二者的活性．结果：MI后4wk存活动物为MI组8只，MI＋卡维地洛组9只，假手术组10只．MI组RVW，LVW／BW，左室舒张末压（LVEDP）、非梗死区CVF均显著升高，MMP-2，MMP-9的表达及其活性亦明显升高（P均〈0．01）；MI＋卡维地洛组与MI组比较，RVW／BW，LVEDP，CVF显著降低（P〈0．05—0．01）．MMP-2，MMP-9表达及活性显著减弱（P〈0．05～0．01）．结论：卡维地洛缓解了MI后心肌细胞外基质的重构，其机制可能与对MMPs的表达和活性调节有关．
AIM： To investigate the effect on myocardial extra- cellular matrix remodeling and matrix metalloproteinases （MMPs） after myocardial infarction （MI） in rabbits by carvedilol which is third-generation β adrenoceptor antagonist, METHODS： Thirtysix New Zealand white rabbits were randomized to 3 groups （n = 12）： MI group, MI ＋ carvedilol group and sham-operation group. The models of MI were induced by ligation of left ventricular branch; the sham-operation group was made by the same procedure but no ligation. The rabbits were killed 4 weeks after operation to examine hemodynamic parameters, body weight （BW） , left and right ventricular weight （LVW, RVW）. Collagen volume fraction （ CVF ） was measured by using Van Gieson （VG） in noninfarcted region; the protein expressions of matrix metalloproteinase 2 （MMP-2） and matrix metalloproteinase 9 （ MMP-9 ） were detected by immunohistochemical analysis in noninfarcted myocardium, and the MMPs activities were assessed bv zymography. RESULTS： At week 4 after MI, there were 8 rabbits left in MI group, 9 in MI ＋ carvedilol group and 10 in sham-operation group. Compared with the sham-operation group, RVW/BW, LVW/BW, left ventricular end-diastolic pressure （LVEDP） and CVF were increased significantly, and expressions and activities of MMP-2 and MMP-9 were enhanced in noninfarcted myocardium of MI group （ P 〈 0.01 ）. Compared with the MI group, RVW/BW, LVEDP and CVF were decreased significantly （P 〈0.05 -0.01 ） , and expressions and activities of MMP-2 and MMP-9 were weakened in the MI ＋ carvedilol group （P〈0.05 - 0.01 ）. CONCLUSION： Carvedilol can prevent myocardial extracellular matrix remodeling, which is associated with the attenuation of myocardial MMP-2 and MMP-9 expressions and activities.
出处
《第四军医大学学报》
北大核心
2006年第15期1384-1387,共4页
Journal of the Fourth Military Medical University
关键词
卡维地洛
细胞外基质
基质金属蛋白酶
carvedilol
extracellular matrix
matrix metalloproteinases
